It has been over 25 years since mercury-203 labeled chlormerodrin was first used as an infarct-avid scintigraphic agent and the era of cardiovascular nuclear imaging began. It was not until the mid-1970's however, that imaging equipment and radiopharmaceuticals were advanced enough to make myocardial imaging a clinical reality. Technetium-99m tetracycline and technetium-99m stannous pyrophosphate were the first clinically useful infarct-avid scintigraphic radiopharmaceuticals developed. Almost simultaneously, potassium-43 was developed as the prototype myocardial perfusion tracer. Thereafter, thallium-201 imaging replaced potassium-43 for myocardial imaging, and this technique has become one of the most widely utilized procedures in nuclear medicine.
Throughout the development of the field of nuclear cardiology, particular attention has been paid to imaging myocardial necrosis. In general terms, this can be accomplished either with a "cold spot" tracer, such as thallium-201, or with a "hot spot" tracer, such as technetium-99m pyrophosphate. Technetium-99m stannous pyrophosphate and related phosphate compounds are routinely used for bone scintigraphy. Technetium-99m stannous pyrophosphate has also been utilized to image myocardial infarction in man. During the past 10 years, this radiopharmaceutical has been studied extensively by many investigators. Initial enthusiasm has waned, and the use of pyrophosphate imaging has diminished substantially over the ensuing years. While highly sensitive for Q-wave myocardial infarction, its clinical utility in patients with non Q-wave infarction or those with smaller myocardial infarcts is open to question. In addition, in order to achieve a sufficiently high sensitivity, the specificity drops significantly. Even with 10 years of history, the clinical significance of diffuse, mild to moderate uptake has not been elucidated fully. In a multicenter investigation limitation of infarct size (MILIS) sponsored by the National Heart, Lung, and Blood Institute, technetium-99m pyrophosphate imaging was included in the evaluation of all patients. In this prospective study of 726 patients with pain presumably caused by irreversible myocardial ischemia and associated with electrocardiographic changes, pyrophosphate imaging had a maximal sensitivity of 91% but a specificity of only 64%.
As a "hot spot" tracer, pyrophosphate displays the area of abnormality on a scintigraphic scan as an area of increased radionuclide uptake. On the other hand, thallium-201 displays abnormalities as "cold spots" or areas of diminished perfusion. These defects can be due to either transient ischemia or infarction, which are virtually indistinguishable on the resting and exercise thallium-201 studies. While thallium-201 imaging is highly sensitive for the detection of irreversible ischemia, especially when performed within the first six hours following the onset of chest pain, this technique cannot differentiate old from new irreversible myocardial damage. In addition, the size of perfusion defects decrease over time, such that the sensitivity of this technique for detection of myocardial infarction or ischemia is time-dependent. In fact, the extent of abnormalities seen on the resting thallium-201 study decreases significantly over the first 48 hours following infarction. Because of these known limitations, neither technetium-99m stannous pyrophosphate imaging nor thallium-201 imaging is routinely utilized in the patient with chest pain necessitating admission to the coronary care unit. Although of definite clinical utility in certain patients, these techniques cannot adequately address the primary questions being posed in the management of unstable ischemic heart disease.